title: 17β-Estradiol alters oxidative stress response protein expression and oxidative damage in the uterus.
abstract: The steroid hormone 17β-estradiol (E2) has profound effects on the uterus. However, with the E2-induced increase in uterine cell proliferation and metabolism comes increased production of reactive oxygen species (ROS). We examined the expression of an interactive network of oxidative stress response proteins including thioredoxin (Trx), Cu/Zn superoxide dismutase (SOD1), apurinic endonuclease (Ape1), and protein disulfide isomerase (PDI). We demonstrated that treatment of ovariectomized C57BL/6J female mice with E2 increased the mRNA and protein levels of Trx, but decreased SOD1 and Ape1 mRNA and protein expression. In contrast, E2 treatment increased PDI protein levels but had no effect on PDI transcript levels. Interestingly, E2 treatment also increased two markers of cellular damage, lipid peroxidation and protein carbonylation. Our studies suggest that the decreased expression of SOD1 and Ape1 caused by E2 treatment may in the long term result in disruption of ROS regulation and play a role in endometrial carcinogenesis.
authors.affiliation: Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States.
authors.forename: Lisi
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States.
authors.forename: Alicia K
authors.initials: AK
authors.lastname: Dietrich
authors.affiliation: Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States. Electronic address: anardull@life.uiuc.edu.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Nardulli
mesh_terms: D000818:Animals; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009821:Oils / Q000494:pharmacology; D010052:Ovariectomy; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D050050:Protein Carbonylation / Q000187:drug effects; D019704:Protein Disulfide-Isomerases / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D011980:Receptors, Progesterone / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology
chemical_list: D047628:Estrogen Receptor alpha; D009821:Oils; D011980:Receptors, Progesterone; D004958:Estradiol; D013879:Thioredoxins; D013482:Superoxide Dismutase; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D019704:Protein Disulfide-Isomerases
keywords: Apurinic endonuclease; Cu/Zn superoxide dismutase; Estrogen receptor ɑ; Oxidative stress; Protein disulfide isomerase; Thioredoxin